Radical relay cyclization/C-C bond formation of allyloxy-tethered aryl iodides with quinoxalin-2(1H)-ones via polysulfide anion photocatalysis.

A visible-light-induced radical relay cyclization/C-C bond formation of quinoxalin-2(1H)-ones with allyloxy-tethered aryl iodides using polysulfide anions as a photocatalyst is described. This protocol allows efficient access to a variety of complicated molecules bearing both quinoxalin-2(1H)-one and 2,3-dihydrobenzofuran motifs in high yields under mild reaction conditions with a broad range of substrates.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastases from gastrointestinal stromal tumors.

OBJECTIVES: This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). METHODS: Between March 2011 and November 2022, 34 patients (16 males; age range, 25-72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1-5.2) cm. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. RESULTS: For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0-45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8-159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. CONCLUSIONS: Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.

Crohn's disease in hemophilic arthropathy patient: a case report.

Crohn's disease (CD) is an inflammatory bowel disease affecting the digestive tract, the incidence of which is on the rise worldwide. The most common clinical manifestation of hemophilia is arthropathy secondary to recurrent joint effusions and chronic synovitis. This article reports on a rare 25-year-old male patient with both hemophilic arthropathy and Crohn's disease who was at risk for pathogenic gastrointestinal bleeding. After undergoing endoscopic pathologic testing and genetic testing, a multidisciplinary expert work-up of a treatment and nutritional plan was performed. The patient improved clinically and adhered to conservative treatment. This case report is the first report of this rare co-morbidity, demonstrating the highly pathogenic mutation locus and summarizing the clinical experience of early diagnosis and treatment.

Molecular transformation of dissolved organic matter in manganese ore-mediated constructed wetlands for fresh leachate treatment.

The organic matter (OM) and nitrogen in Fresh leachate (FL) from waste compression sites pose environmental and health risks. Even though the constructed wetland (CW) can efficiently remove these pollutants, the molecular-level transformations of dissolved OM (DOM) in FL remain uncertain. This study reports the molecular dynamics of DOM and nitrogen removal during FL treatment in CWs. Two lab-scale vertical-flow CW systems were employed: one using only sand as substrates (act as a control, CW-C) and the other employing an equal mixture of manganese ore powder and sand (experimental, CW-M). Over 488 days of operation, CW-M exhibited significantly higher removal rates for chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), and dissolved organic matter (represented by dissolved organic carbon, DOC) at 98.2 ± 2.5%, 99.2 ± 1.4%, and 97.9 ± 1.9%, respectively, in contrast to CW-C (92.8 ± 6.8%, 77.1 ± 28.1%, and 74.7 ± 9.5%). The three-dimensional fluorescence excitation-emission matrix (3D-EEM) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analyses unveiled that the influent DOM was predominantly composed of readily biodegradable protein-like substances with high carbon content and low unsaturation. Throughout treatment, it led to the degradation of low O/C and high H/C compounds, resulting in the formation of DOM with higher unsaturation and aromaticity, resembling humic-like substances. CW-M showcased a distinct DOM composition, characterized by lower carbon content yet higher unsaturation and aromaticity than CW-C. The study also identified the presence of Gammaproteobacteria, reported as Mn-oxidizing bacteria with significantly higher abundance in the upper and middle layers of CW-M, facilitating manganese cycling and improving DOM removal. Key pathways contributing to DOM removal encompassed adsorption, catalytic oxidation by manganese oxides, and microbial degradation. This study offers novel insights into DOM transformation and removal from FL during CW treatment, which will facilitate better design and enhanced performance.

Pseudostellaria heterophylla improves intestinal microecology through modulating gut microbiota and metabolites in mice.

BACKGROUND: Pseudostellaria heterophylla is a Chinese medicine and healthy edible that is widely used to for its immunomodulatory, antioxidant, antidiabetic and antitussive properties. However, the potential function of P. heterophylla in intestinal microecology remains unclear. In this study, we investigated the impact of P. heterophylla on immune functions and evaluated its potential to regulate the gut microbiota and metabolome. RESULTS: The results showed that P. heterophylla significantly increased the content of red blood cells, total antioxidant capacity and expression of immune factors, and decreased platelet counts when compared to the control under cyclophosphamide injury. In addition, P. heterophylla altered the diversity and composition of the gut bacterial community; increased the abundance of potentially beneficial Akkermansia, Roseburia, unclassified Clostridiaceae, Mucispirillum, Anaeroplasma and Parabacteroides; and decreased the relative abundance of pathogenic Cupriavidus and Staphylococcus in healthy mice. Metabolomic analyses showed that P. heterophylla significantly increased the content of functional oligosaccharides, common oligosaccharides, vitamins and functional substances. Probiotics and pathogens were regulated by metabolites across 11 pathways in the bacterial-host co-metabolism network. CONCLUSION: We demonstrated that P. heterophylla increased the abundance of probiotics and decreased pathogens, and further stimulated host microbes to produce beneficial secondary metabolites for host health. Our studies highlight the role of P. heterophylla in gut health and provide new insights for the development of traditional Chinese medicine in the diet. © 2024 Society of Chemical Industry.

[Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

Electrophilic Halospirocyclization of N-Benzylacrylamides to Access 4-Halomethyl-2-azaspiro[4.5]decanes.

An electrophilic spirocyclization of N-benzylacrylamides with N-halosuccinimides (NXS) as the halogenating reagents has been developed. This reaction is carried out at room temperature under simple conditions without relying on metal reagents, photochemistry, or electrochemistry, providing a fast and efficient route to synthesize a wide variety of 4-halomethyl-2-azaspiro[4.5]decanes with satisfactory yields. The approach is further highlighted through gram-scale synthesis and diverse transformations of the spiro products.

Purple Rehmannia: Investigation of the activation of R2R3-MYB transcription factors involved in anthocyanin biosynthesis.

Engineering anthocyanin biosynthesis in herbs could provide health-promoting foods for improving human health. Rehmannia glutinosa is a popular medicinal herb in Asia, and was a health food for the emperors of the Han Dynasty (59 B.C.). In this study, we revealed the differences in anthocyanin composition and content between three Rehmannia species. On the 250, 235 and 206 identified MYBs in the respective species, six could regulate anthocyanin biosynthesis by activating the ANTHOCYANIDIN SYNTHASE (ANS) gene expression. Permanent overexpression of the Rehmannia MYB genes in tobacco strongly promoted anthocyanin content and expression levels of NtANS and other genes. A red appearance of leaves and tuberous/roots was observed, and the total anthocyanin content and the cyanidin-3-O-glucoside content were significantly higher in the lines overexpressing RgMYB41, RgMYB42, and RgMYB43 from R. glutinosa, as well as RcMYB1 and RcMYB3 in R. chingii and RhMYB1 from R. henryi plants. Knocking out of RcMYB3 by CRISPR/Cas9 gene editing resulted in the discoloration of the R. chingii corolla lobes, and decreased the content of anthocyanin. R. glutinosa overexpressing RcMYB3 displayed a distinct purple color in the whole plants, and the antioxidant activity of the transgenic plants was significantly enhanced compared to WT. These results indicate that Rehmannia MYBs can be used to engineer anthocyanin biosynthesis in herbs to improve their additional value, such as increased antioxidant contents.

Apportioning Atmospheric Ammonia Sources across Spatial and Seasonal Scales by Their Isotopic Fingerprint.

Mitigating ammonia (NH3) emissions is a significant challenge, given its well-recognized role in the troposphere, contributing to secondary particle formation and impacting acid rain. The difficulty arises from the highly uncertain attribution of atmospheric NH3 to specific emission sources, especially when accounting for diverse environments and varying spatial and temporal scales. In this study, we established a refined δ15N fingerprint for eight emission sources, including three previously overlooked sources of potential importance. We applied this approach in a year-long case study conducted in urban and rural sites located only 40 km apart in the Shandong Peninsula, North China Plain. Our findings highlight that although atmospheric NH3 concentrations and seasonal trends exhibited similarities, their isotopic compositions revealed significant distinctions in the primary NH3 sources. In rural areas, although agriculture emerged as the dominant emission source (64.2 ± 19.5%), a previously underestimated household stove source also played a considerably greater role, particularly during cold seasons (36.5 ± 12.5%). In urban areas, industry and traffic (33.5 ± 15.6%) and, surprisingly, sewage treatment (27.7 ± 11.3%) associated with high population density were identified as the major contributors. Given the relatively short lifetime of atmospheric NH3, our findings highlight the significance of the isotope approach in offering a more comprehensive understanding of localized and seasonal influences of NH3 sources compared to emissions inventories. The refined isotopic fingerprint proves to be an effective tool in distinguishing source contributions across spatial and seasonal scales, thereby providing valuable insights for the development of emission mitigation policies aimed at addressing the increasing NH3 burden on the local atmosphere.

Evaluation of the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation for hepatocellular carcinoma and liver metastases adjacent to the gallbladder.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) and liver metastases adjacent to the gallbladder (GB). MATERIALS AND METHODS: A total of 113 patients with 118 liver lesions (63 HCC lesions and 55 liver metastases) adjacent to the gallbladder underwent RFA between March 2011 and June 2019. Gallbladder-related complications and technique effectiveness rates were evaluated based on the classification of liver tumors and the distance between the lesion and the gallbladder. RESULTS: Gallbladder-related complications were observed in 13 patients. Among the patients with HCC, there was no significant difference between the ≤0.5 cm and >0.5 cm groups (p = .282). However, among the patients with liver metastases, the incidence of gallbladder-related complications in the ≤0.5 cm group was significantly higher than that in the >0.5 cm group (p = .025). The overall incidence of complications was significantly higher in the ≤0.5 cm group than in the >0.5 cm group (p = .020). Among the patients with lesions ≤3 cm, the technical effectiveness rate in the HCC group was significantly higher than in the liver metastasis group (p = .036). CONCLUSION: RFA is a safe and effective treatment option for liver tumors adjacent to the gallbladder. Patients with lesions ≤0.5 cm from the gallbladder had higher gallbladder-related complications, especially patients with liver metastases. Among patients with lesions ≤3 cm, RFA showed greater technical effectiveness for treating HCC than for treating liver metastases.

Fast and Efficient Atmospheric NO2 Collection for Isotopic Analysis by a 3D-Printed Denuder System.

Being major species of atmospheric reactive nitrogen, nitrogen oxides (NOx = NO + NO2) have important implications for ozone and OH radical formation in addition to nitrogen cycles. Stable nitrogen isotopes (δ15N) of NOx have been sought to track NOx emissions and NOx chemical reactivities in the atmosphere. The current atmospheric NOx collection methods for isotopic analysis, however, largely suffer from unverified collection efficiency and/or low collection speed (<10 L/min). The latter makes it difficult to study δ15N(NOx) in pristine regions with low NOx concentrations. Here, we present a three-dimensional (3D)-printed honeycomb denuder (3DP-HCD) system, which can effectively collect atmospheric NO2 (a major part of NOx) under a variety of laboratory and field conditions. With a coating solution consisting of 10% potassium hydroxide (KOH) and 25% guaiacol in methanol, the denuder system can collect NO2 with nearly 100% efficiency at flow rates of up to 70 L/min, which is 7 times higher than that of the existing method and allows high-resolution (e.g., diurnal or finer resolution) NO2 collection even in pristine sites. Besides, the δ15N of NO2 collected by the 3DP-HCD system shows good reproducibility and consistency with the previously tested method. Preliminary results of online NO oxidation by a chrome trioxide (CrO3) oxidizer for simultaneous NO and NO2 collection are also presented and discussed.

A Multicenter Randomized Controlled Study of Contrast-enhanced US versus US-guided Biopsy of Focal Liver Lesions.

Background Retrospective or single-center prospective studies with relatively small samples have shown that contrast-enhanced US (CEUS) can improve the diagnostic accuracy of percutaneous biopsy, but larger prospective studies are lacking. Purpose To assess the diagnostic performance of CEUS-guided biopsy (CEUS-GB) of focal liver lesions (FLLs) compared with US-guided biopsy (US-GB) in a prospective multicenter study. Materials and Methods In this randomized controlled study conducted in nine hospitals in China between March 2016 and August 2019, adult participants with FLLs detected with US, CT, or MRI and planned for percutaneous biopsy were randomly assigned to undergo either US-GB or CEUS-GB. Lesions diagnosed as malignant at histopathologic analysis were considered true-positive findings. Benign or indeterminate lesions required further confirmation with either repeat biopsy or clinical follow-up at 6 months or later. The primary endpoint was the diagnostic accuracy rate, and comparison between groups was made using the χ2 test. Results In this study, 2056 participants (1297 men, 759 women; mean age, 58 years ± 11 [SD]) were analyzed: 1030 underwent biopsy with US guidance and 1026 underwent biopsy with CEUS guidance. The overall diagnostic accuracy rate of CEUS-GB was 96% (983 of 1026) versus 93% (953 of 1030) for US-GB (P = .002), CEUS-GB enabled correct identification in 96% of participants (983 of 1026) compared with 92% (953 of 1030) with US-GB (P = .002). The negative predictive value (NPV) for both biopsy methods was moderate but significantly higher for CEUS-GB than for US-GB (74% vs 57%, P = .001). The difference was remarkable for lesions smaller than 2.0 cm, with CEUS-GB showing higher diagnostic accuracy (96% vs 88%, P = .004) and sensitivity (95% vs 87%, P = .007) than US-GB. Among lesions smaller than 2.0 cm, the accuracy of CEUS-GB and US-GB for detection of hepatocellular carcinoma was 93% and 80%, respectively (P = .008), while it was comparable for liver metastases (98% vs 95%, P = .63). Conclusion Contrast-enhanced US-guided biopsy of focal liver lesions is an effective and safe procedure with a higher diagnostic accuracy than US-guided biopsy, especially for lesions smaller than 2.0 cm and for hepatocellular carcinoma diagnosis. Clinical trial registration no. NCT02413437 © RSNA, 2022 Online supplemental material is available for this article.

Morphogenesis, ultrastructure, and chemical profiling of trichomes in Artemisia argyi H. Lév. & Vaniot (Asteraceae).

MAIN CONCLUSION: Glandular trichomes of Artemisia argyi H. Lév. & Vaniot are the key tissues for the production of flavonoid and terpenoid metabolites. Artemisia argyi H. Lév. & Vaniot is an herbaceous perennial plant that has been widely used in traditional medicine for thousands of years. Glandular trichomes (GTs) and nonglandular trichomes (NGTs) have been reported on the leaf surface of A. argyi. The aim of this study was to elucidate the morphogenetic process and to analyze the metabolites of trichomes in A. argyi. The morphogenesis of GTs and NGTs was characterized using light, scanning, and transmission electron microscopy. The constituents of GTs were analyzed using laser microdissection combined with gas and liquid chromatography-mass spectrometry. Five developmental stages of two types of GTs and four developmental stages of one type of NGTs were observed. Two types of mature GT and one type of NGT were composed of 10, 5, and 4-6 cells, respectively. A large storage cavity was detected between the cuticle and cell walls in the first type of mature GT. Large nuclei, nucleoli, and mitochondria were observed in the basal and intermediate cells of the second type of GT. In addition, large vacuoles were observed in the basal and apical cells, and large nuclei were observed in the middle cells of NGTs. One monoterpene and seven flavonoids were identified in GTs of A. argyi. We suggest that GTs are the key tissues for the production of bioactive metabolites in A. argyi. This study provides an important theoretical basis and technical approach for clarifying the regulatory mechanisms for trichome development and bioactive metabolite biosynthesis in A. argyi.

LncRNA embryonic stem cells expressed 1 (Lncenc1) is identified as a novel regulator in neuropathic pain by interacting with EZH2 and downregulating the expression of Bai1 in mouse microglia.

LncRNA embryonic stem cells expressed 1 (Lncenc1), named after its high expression in naïve embryonic stem cells (nESCs), has been rarely studied in almost all pathological processes. Evidences suggest that Lncenc1 is likely to work in the form of RNA-protein complex. Here, we found that Lncenc1 in dorsal root ganglion (DRG) was significantly upregulated in response to mouse nerve injury caused by partial sciatic nerve ligation (pSNL). Overexpression of Lncenc1 mediated by adenoviral expression vector promoted the activation of microglia and the production of inflammatory cytokines including TNF-α, IL-1ß and MCP-1. In contrast, knockdown of Lncenc1 suppressed activation of microglia and production of inflammatory cytokines. In the mechanism exploration, we found that Lncenc1 could bind with the RNA binding protein (RBP) enhancer of zeste homologue 2 (EZH2), an identified contributor in microglial activation and neuropathic pain. Lncenc1 interacted with EZH2 and downregulated the expression of brain-specific angiogenesis inhibitor 1 (BAI1). Either inhibition of EZH2 or overexpression of BAI1 could reverse the effects of Lncenc1 overexpression on microglial activation and neuroinflammation. Finally, the Lncenc1-siRNA was intrathecally injected into pSNL mice, and its effects on neuropathic pain were evaluated. Knockdown of Lncenc1 attenuated the development and maintenance of mechanical and thermal hyperalgesia of pSNL mice, accompanied by an increase in BAI1 expression and decrease in inflammatory cytokines. In conclusion, Lncenc1 contributes to neuropathic pain by interacting with EZH2 and downregulating the BAI1 gene in mouse microglia.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastasis from pancreatic adenocarcinoma.

OBJECTIVE: To analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for pancreatic adenocarcinoma liver metastasis (PALM). METHODS: Between January 2010 and July 2021, 20 patients (13 males) with an average age of 58.9 ± 11.7 years who underwent RFA for PALM were included. The mean maximum diameter of PALMs was 2.6 ± 1.1 cm (1.0-6.0 cm). Survival curves were built using the Kaplan-Meier method and compared by the log-rank test. Multivariable analyses were performed by using the Cox proportional hazards model. RESULTS: Twenty patients with 29 PALMs underwent 23 RFA sessions. Technical efficacy was achieved in 28 PALMs (28/29, 96.6%). The mean overall survival (OS) after RFA was 14.6 months and the 1-, 2-year survival rates were 39.5%, 18.1%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.023) and extrahepatic metastasis before RFA (p = 0.038) were identified as independent prognostic factors for OS in patients with PALM. Additionally, the mean progression-free survival (PFS) after RFA was 11.5 months and 1-, 2- year survival rates were 26.0%, 17.3%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.016) and extrahepatic metastasis before RFA (p = 0.043) were also identified as independent prognostic factors for PFS in patients with PALM. CONCLUSION: RFA is a safe and effective treatment for patients with PALM, especially in patients with normal serum level of CA199 or the patients without extrahepatic metastases before RFA.

Multi-omics analyses revealed key factors involved in fluorescent carbon-dots-regulated secondary metabolism in Tetrastigma hemsleyanum.

BACKGROUND: Luminescent nanomaterials (LNMs), especially newly-exploited fluorescent carbon-dots (CDs), have demonstrated promising candidates for sunlight harvesting and enhanced photosynthesis efficiency of crops. However, most of the studies focus on the design and synthesis of LNMs and primary metabolism in biomass acceleration, secondary metabolism that closely associated with the quality ingredients of plants is rarely mentioned. RESULTS: UV-absorptive and water-soluble NIR-CDs were harvested via a facile microwave-assisted carbonization method. The effect and regulatory mechanism of NIR-CDs on the secondary metabolism and bioactive ingredients accumulation in Tetrastigma hemsleyanum were explored. A total of 191 differential secondary metabolites and 6874 differentially expressed genes were identified when the NIR-CDs were adopted for enhancing growth of T. hemsleyanum. The phenolic acids were generally improved, but the flavonoids were more likely to decrease. The pivotal differentially expressed genes were involved in biosynthesis of secondary metabolites, flavonoid biosynthesis, porphyrin and chlorophyll metabolism, etc. The gene-metabolite association was constructed and 44 hub genes highly related to quality ingredients accumulation and growth were identified, among which and the top 5 genes of the PPI network might be the key regulators. CONCLUSION: This research provided key regulatory genes and differentially accumulating quality ingredients under NIR-CDs-treatment, which could provide a theoretical basis for expanding the applications of nanomaterial in industrial crop agriculture.

[Identification and biological characteristics of a pathogen causing leaf blight of Rehmannia glutinosa].

Leaf blight outbroke in Rehmannia glutinosa plantation in Wenxian county, Henan province in 2019. R. glutinosa plants with diseased leaves were collected from the plantation, and three strains were isolated from the diseased leaf samples. Pathogenicity test, morphological observation, and phylogenetic analysis of ITS, EF1-α, and Tub suggested that they were respectively Fusarium proliferatum, F. oxysporum, and F.acuminatum. Among them, F. acuminatum, as a pathogen of R. glutinosa leaf disease, had never been reported. To clarify the biological characteristics of F. acuminatum, this study tested the influence of light, pH, temperature, medium, carbon source, and nitrogen source on the mycelial growth rate of the pathogen during a 5-day culture period, and explored the lethal temperature. The results showed that the mycelia grew well under the photoperiod of 12 h light/12 h darkness, at 5-40 ℃(optimal temperature: 25 ℃), at pH 4-11(optimal pH: 7.0), on a variety of media(optimal medium: oatmeal agar), and in the presence of diverse carbon and nitrogen sources(optimal carbon source: soluble starch; optimal nitrogen source: sodium nitrate). The lethal temperature was verified to be 51 ℃(10 min). The conclusion is expected to lay a scientific basis for diagnosis and control of R. glutinosa leaf diseases caused by F. acuminatum.

Integrated transcriptome and small RNA sequencing analyses reveal a drought stress response network in Sophora tonkinensis.

BACKGROUND: Sophora tonkinensis Gagnep is a traditional Chinese medical plant that is mainly cultivated in southern China. Drought stress is one of the major abiotic stresses that negatively impacts S. tonkinensis growth. However, the molecular mechanisms governing the responses to drought stress in S. tonkinensis at the transcriptional and posttranscriptional levels are not well understood. RESULTS: To identify genes and miRNAs involved in drought stress responses in S. tonkinensis, both mRNA and small RNA sequencing was performed in root samples under control, mild drought, and severe drought conditions. mRNA sequencing revealed 66,476 unigenes, and the differentially expressed unigenes (DEGs) were associated with several key pathways, including phenylpropanoid biosynthesis, sugar metabolism, and quinolizidine alkaloid biosynthesis pathways. A total of 10 and 30 transcription factors (TFs) were identified among the DEGs under mild and severe drought stress, respectively. Moreover, small RNA sequencing revealed a total of 368 miRNAs, including 255 known miRNAs and 113 novel miRNAs. The differentially expressed miRNAs and their target genes were involved in the regulation of plant hormone signal transduction, the spliceosome, and ribosomes. Analysis of the regulatory network involved in the response to drought stress revealed 37 differentially expressed miRNA-mRNA pairs. CONCLUSION: This is the first study to simultaneously profile the expression patterns of mRNAs and miRNAs on a genome-wide scale to elucidate the molecular mechanisms of the drought stress responses of S. tonkinensis. Our results suggest that S. tonkinensis implements diverse mechanisms to modulate its responses to drought stress.

The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for limited hepatocellular carcinoma (HCC), the efficacy of this treatment for recurrent HCC has not been thoroughly investigated. Purpose To compare the long-term outcomes and analyze the prognostic factors for outcomes after RFA for initial HCC versus as a second-line treatment for recurrent HCC. Materials and Methods This retrospective study included 560 patients with solitary tumors 5 cm or smaller (263 initial HCCs, 297 -recurrent HCCs) who underwent percutaneous US-guided RFA from January 2005 to December 2016. Of 297 patients with -recurrent HCC, 134 had previously undergone hepatectomy, 128 had undergone transarterial chemoembolization (TACE), and 35 had undergone local ablation therapy. Overall survival (OS) between initial HCC and recurrent HCC was compared before and after propensity score matching. Prognostic factors for all patients were analyzed with the log-rank test and Cox proportional hazards model. Results A total of 560 patients (mean age, 60 years ± 12 [standard deviation]; 441 men) were evaluated. Before matching, the OS rates at 1, 3, 5, and 10 years were 92.6%, 73.9%, 59.3%, and 39.6%, respectively, in patients with recurrent HCC and 92.8%, 75.4%, 63.3%, and 44.7% in patients with initial HCC (P = .27). After matching, the OS rates at 1, 3, 5, and 10 years were 94.8%, 75.7%, 61.6%, and 47.3% in the initial HCC group and 91.9%, 71.2%, 58.7%, and 45.2% in the recurrent HCC group (P = .32). Among patients with recurrent HCC, no significant difference in mean OS was noted for local recurrence versus distant recurrence (81.6 months ± 5.1 vs 83.8 months ± 6.6, P = .82) or previous treatment modality (82.0 months ± 7.3 in the resection group, 82.7 months ± 5.3 in the TACE group, and 79.3 months ± 10.8 in the local ablation group; P = .83). Local tumor progression after previous local ablation (10 of 35 [28.6%]) was higher than that after previous hepatectomy (15 of 134 [11.2%], P = .04). Multivariable analysis demonstrated that tumor size (hazard ratio, 1.58; 95% CI: 1.06, 2.36; P = .02), portal hypertension (hazard ratio, 1.52; 95% CI: 1.03, 2.26; P = .04), Child-Pugh class (hazard ratio, 2.01; 95% CI: 1.02, 3.96; P = .045), and serum α-fetoprotein level (hazard ratio, 1.62; 95% CI: 1.10, 2.39; P = .01) were independent predictive factors for recurrent HCC outcomes. Conclusion Radiofrequency ablation provides similar long-term survival for solitary hepatocellular carcinoma of 5 cm or less, regardless of whether treatment is initial or salvage therapy. © RSNA, 2021 Online supplemental material is available for this article.